DESCRIPTION (Applicant's Abstract): While it is well known that hemispheric strokes can disrupt function of the non-lesioned hemisphere, the mechanisms of this disruption are poorly understood. Accordingly, the specific aims of the proposed research are 1) to develop computer models of hemispheric interactions and asymmetries, using them to systematically study factors influencing laterlization of function, and 2) to study the effects of acute focal lesion sin these models, determining factors influencing recovery and how they might by manipulated to maximize recovery. Thus, this work will introduce a new computational approach to studying hemispheric specialization and transcallosal diaschisis in stroke that complements more traditional human and animal experimental work. The neural models created in this research will consist of paired, interconnected hemispheric regions involving sensorimotor tasks and a linguistic task. Although simplified from biological reality, these computational models are based on generally accepted principles of cortical connectivity, dynamics and plasticity. They will be used to examine which of several contemporary hypotheses about the biological mechanisms of hemispheric specialization produce functional lateralization when tested in a detailed computational brain model. Specifically, we will examine asymmetries in the size, connectivity , excitability, plasticity, etc. of model hemisphere regions and different assumptions about the role of the corpus callosum (inhibitory versus excitatory, etc.). Selected versions of these models will then be subjected to simulated acute focal lesions of varying sizes and location s to assess which model assumptions and lesions lead to transcallosal diaschisis. Particular emphasis will be placed on identifying model features that can be varied to maximize post-lesion recovery. To our knowledge, this is the first attempt to develop computational models of hemispheric specialization and transcallosal diaschisis. Preliminary simulations have clearly demonstrated the feasibility of the proposed work. These models will allow systematic exploration of the mechanisms underlying hemispheric functional asymmetries and post-stroke recovery, and may suggest news therapeutic concepts for stroke patients.